Effect of lockdown amid second wave of COVID-19 on environmental noise scenario of the megacity Delhi, India.

This paper analyzes the impact of second wave of COVID-19 lockdown on environmental noise levels of 25 sites in Delhi city and compares the noise scenario during pre-lockdown, lockdown, and post-lockdown periods. The study utilized the noise monitoring data acquired from 25 real-time ambient noise monitoring stations, installed by the Delhi Pollution Control Committee, Delhi, at various sites throughout Delhi city. A significant reduction of up to 10 and 3 dB(A) in day and night equivalent noise levels, respectively, had been observed during the lockdown period as compared to the pre-lockdown and post-lockdown periods. The study also revealed that only nine sites, including four industrial and five commercial zone sites, complied with the ambient noise standards during lockdown period, and no silence or residential zone sites complied with the ambient noise standards even during the lockdown period. A roadmap for environmental noise management and control is suggested. The study also reports the community's perception toward the change in acoustic environment of Delhi city during the lockdown period by conducting an environmental noise perception survey. The present study should be helpful in devising noise control action plans and policy interventions for environmental noise management and control in the metropolitan city Delhi, India.

Assessing retinal ganglion cell damage.

Retinal ganglion cell (RGC) loss is the hallmark of optic neuropathies, including glaucoma, where damage to RGC axons occurs at the level of the optic nerve head. In experimental glaucoma, damage is assessed at the axon level (in the retinal nerve fibre layer and optic nerve head) or at the soma level (in the retina). In clinical glaucoma where measurements are generally limited to non-invasive techniques, structural measurements of the retinal nerve fibre layer and optic nerve head, or functional measurements with perimetry provide surrogate estimates of RGC integrity. These surrogate measurements, while clinically useful, are several levels removed from estimating actual RGC loss. Advances in imaging, labelling techniques, and transgenic medicine are making enormous strides in experimental glaucoma, providing knowledge on the pathophysiology of glaucoma, its progression and testing new therapeutic avenues. Advances are also being made in functional imaging of RGCs. Future efforts will now be directed towards translating these advances to clinical care.

Rates of glaucomatous visual field change after trabeculectomy.

BACKGROUND: Trabeculectomy is frequently performed in patients with glaucoma who are deteriorating, although its effects on rates of visual field (VF) progression are not fully understood. We studied the rate of VF progression post trabeculectomy comparing with medically treated patients matched for VF loss. METHODS: Medical records of patients who underwent trabeculectomy alone or combined with cataract extraction were reviewed. Patients with 5 or more 24-2 VF examinations post trabeculectomy were selected. The rate of mean deviation (MD) change after surgery was calculated for each patient. These patients were pairwise matched based on baseline MD with patients with glaucoma who were treated medically and had at least 5 VF tests. RESULTS: 180 surgical patients were identified and matched with 180 medically treated patients (baseline MD of -8.72 (5.24) dB and -8.71 (5.22) dB, respectively). Surgically and medically treated patients were followed for 7.4 (2.9) and 6.8 (3.1) years respectively. The MD slopes were -0.22 (0.55) dB/year and -0.08 (1.10) dB/year in the surgically and medically treated patients, respectively, and not statistically different (p=0.13, 95% CI -0.31 to 0.04). More patients in the surgical group had fast progression (rates worse than -1 dB/year) than in the medical group (17 and 7 patients, respectively, p=0.05). CONCLUSIONS: Our findings suggest that most patients who undergo trabeculectomy demonstrate relatively slow rates of VF progression postoperatively, similar to patients treated medically, although some patients can continue to progress despite adequate surgical control of intraocular pressure.

Characterization of functional trait diversity among Indian cultivated and weedy rice populations.

Weedy rice, a menace in rice growing areas globally, is biosimilar having attributes similar to cultivated and wild rice, and therefore is difficult to manage. A study was initiated to characterize the functional traits of 76 weedy rice populations and commonly grown rice cultivars from different agro-climatic zones for nine morphological, five physiological, and three phenological parameters in a field experiment under an augmented block design. Comparison between weedy and cultivated rice revealed a difference in duration (days) from panicle emergence to heading as the most variable trait and awn length as the least variable one, as evidenced from their coefficients of variation. The results of principal component analysis revealed the first three principal components to represent 47.3% of the total variation, which indicates an important role of transpiration, conductance, leaf-air temperature difference, days to panicle emergence, days to heading, flag leaf length, SPAD (soil-plant analysis development), grain weight, plant height, and panicle length to the diversity in weedy rice populations. The variations existing in weedy rice population are a major reason for its wider adaptability to varied environmental conditions and also a problem while trying to manage it.

Clarithromycin enhances the antimalarial efficacy of mefloquine via its increased bioavailability and disrupting P. falciparum apicoplast.

AIM: Many important drugs like mefloquine are not being used because of the development of resistance and other related issues. In the present study, we aimed to control drug resistance by using combination therapy and tried to understand the mechanism involved. MATERIAL AND METHODS: We have explored in vitro interaction of clarithromycin (CLTR), and mefloquine (MQ) against Pf3D7 and PfK1 strains. Bioavailability of MQ in parasitized RBC lysate was checked in the presence/absence of CLTR using HPLC method. Further tufA mRNA/protein expression was investigated to know the effect of both drugs on apicoplast by using qPCR and Western blotting. KEY FINDINGS: MQ and CLTR inhibited growth of Pf3D7 and PfK1. CLTR showed its delayed antimalarial effect by its low IC50 values in the second cycle which indicates its effect on apicoplast. Downregulation of tufA expression on both mRNA and protein level supports this hypothesis. MQ and CLTR showed synergism/additiveness (mean ∑FICs = 0.89 and 1.26) against Pf3D7 and PfK1 respectively. It is evidenced from HPLC data that CLTR might have reduced metabolism of MQ in Plasmodium falciparum, leading to increased levels of MQ to produce enhanced antimalarial activity. The metabolism of CLTR is also reduced may be due to competitive metabolism of MQ via CYP3A4. SIGNIFICANCE: The present study reveals that broad spectrum biological activities (i.e. antimalarial and antiviral) of MQ can be saved by using suitable partner drug like CLTR. This study also shows that CLTR increases the concentration of MQ and disrupts the apicoplast.

To study the role of antibiotic+steroid irrigation of the middle ear in active chronic otitis media with small perforation and pulsatile discharge.

OBJECTIVE: To evaluate the usefulness of antibiotic+steroid irrigation of the middle ear in patients with otitis media with small perforation and pulsatile discharge. METHOD: A prospective, randomised, evaluator-blinded study was carried at a single tertiary care centre over eight years, looking at 100 patients with chronic suppurative otitis media involving small tympanic membrane perforations and pulsatile mucopurulent discharge. The patients were randomised and divided into two groups. In group A, the examination under microscope, with suction cleaning of the external canal, was followed by irrigation of the middle ear with antibiotic+steroid solution for up to one week, while group B was prescribed self-administration of the same drops with systemic antibiotics. The patients were followed up daily for 10 days to monitor otorrhoea relief and on a weekly basis subsequently to monitor the healing of the tympanic membrane. RESULTS: Forty-nine patients in group A had a dry ear after 3-7 days of daily suction and the irrigation of middle ear with the antibiotic+steroid solution and 44 had a healed tympanic membrane after an average three months of follow-up. Five patients with dry ear but persistent perforation underwent tympanoplasty, while only one patient with a persistent ear discharge underwent mastoid exploration. In group B, eight patients on oral antibiotics and self-administration of the same drops had dry ear while 34 had dry ear after receiving intravenous antibiotics. Thirty perforations healed spontaneously and 12 required tympanoplasty. In 8 patients, the tympano-mastoid was explored and these patients had dry, hearing ears only after surgery. CONCLUSION: Patients with chronic suppurative otitis media involving small perforations and pulsatile discharge can be managed conservatively with simple suction cleaning + middle ear irrigation with antibiotics + steroid drops.

Design and synthesis of 6,7-dimethoxyquinazoline analogs as multi-targeted ligands for α1- and AII-receptors antagonism.

Multiple-targeted ligands can have certain advantages for the management of hypertension which has multiple controls. Molecules with dual bioactivities are available in literature for treating metabolic disorders like diabetes, hypertension and hypercholesterolemia. After scrutinizing the SAR of prazosin-type α1-blockers and AII-antagonists it was planned to develop dual α1- and AII-antagonists. Five series of quinazoline derivatives were synthesized and evaluated as dual α1- and AII-antagonists on rat aortic strips for the blockade of known α1- and AII-agonist mediated contractions. Many compounds showed balanced activity on both the receptors but compound (22) was found to be the most active derivative having higher antagonistic activity on both the receptors. In the in vivo experiments the chosen compound (22) was slightly less active than prazosin but was found to be equipotent to losartan. These findings shed a new light on the structural requirements for both α1- as well as AII-receptor antagonists.

Determination of orbifloxacin in sheep plasma by high performance liquid chromatography with ultraviolet detection after intravenous and intramuscular administration.

INTRODUCTION: Single-dose pharmacokinetics of orbifloxacin (2.5mg/kg body weight) were determined in clinically normal female Patanwadi sheep (n=6) following intravenous and intramuscular administration. METHODS: Orbifloxacin concentrations were determined by high performance liquid chromatography with ultraviolet detection. The concentration-time data were analyzed by non-compartmental kinetic method. RESULTS AND DISCUSSION: Following a single intravenous injection, an elimination half-life (t(1/2ß)) of 8.31±0.102h. Steady-state volume of distribution (Vd(ss)) and total body clearance (Cl(B)) were 3.09±0.282L/kg and 0.158±0.006L/kg/h, respectively. Following intramuscular administration, an elimination rate constant (ß), the area under the curve from zero to infinity (AUC(0-∞)) and the mean absorption time (MAT) were 0.015±0.001h(-1), 23.49±1.722µg·h/mL and 7.50±0.58h, respectively. The peak plasma concentration (C(max)) of 1.81±0.005µg/mL was achieved at 1.00±0.00h. The mean residence time (MRT) was 26.25±1.083h and the absolute bioavailability was 150.8±12.35%, respectively. Orbifloxacin could be useful for the treatment of bacterial infections in sheep that are sensitive to this drug.

Rates of retinal nerve fibre layer thickness change in glaucoma patients and control subjects.

PURPOSE: To examine the rates of retinal nerve fibre layer thickness (RNFLT) change in glaucoma patients and healthy, age-similar control subjects with three techniques: scanning laser polarimetry with variable corneal compensation (VCC) and enhanced corneal compensation (ECC), and time-domain optical coherence tomography (OCT). METHODS: Sixty-one patients and thirty-three controls were examined with each technique and with standard automated perimetry (SAP) every 6 months. Rates of global RNFLT change and SAP mean deviation (MD) change were estimated with linear mixed-effects models. RESULTS: The median (interquartile range) baseline age was 64.4 (58.2, 71.0) years for patients and 62.4 (56.3, 70.1) years for controls (P=0.56). There was a median of seven examinations over 3.1 years for patients and six examinations in 3.0 years for controls. Baseline visual field MD and RNFLT for all imaging modalities were significantly lower (P<0.01) in patients compared with controls. Rates of RNFLT change were not significantly different between patients and controls (P≥0.19). Mean rates of VCC-measured RNFLT change were -0.18 and -0.37 µm per year in patients and controls, whereas the respective figures for ECC and OCT were -0.13 and -0.31 µm per year, and 0.04 and 0.61 µm per year. Mean rates of MD change were -0.20 and 0.03 dB per year in patients and controls, respectively (P=0.01). CONCLUSION: Rates of RNFLT change in glaucoma patients were not statistically different from control subjects for any modality. A significantly negative rate of MD change in patients suggests a genuine, continued deterioration in these patients not reflected by RNFLT changes.

Analysis and antimicrobial activity of volatile constituents from Quercus leucotrichophora (Fagaceae) bark.

The chemical composition of the volatile extract (yield ≈ 0.13%, v/w) from the bark of Quercus leucotrichophora (Fagaceae) was analysed for the first time by GC-MS. Twenty-three constituents, amounting to 93.0% of the total detected contents of the volatile extract, were identified. The volatile extract contained approximately 86.36% monoterpenoids, 6.53% sesquiterpenoids and 0.11% aliphatic aldehydes. 1,8-Cineol (40.359%) followed by γ-terpinene (16.369%) were the major monoterpene constituents of the volatile extract. The residue of volatile extract (0.00025-250 µg mL(-1)) exhibited a potent antimicrobial activity against Streptococcus pyogenes ATCC 19615. This study concludes that residues of the volatile extract of Q. leucotrichophora could serve as an important bioresource for the extraction and isolation of monoterpenoids exhibiting antimicrobial activity, and thus has good potential for use in the pharmaceutical industry.

Comparative study of complete nasal packing with and without airways.

OBJECTIVE: To study and compare the effects of complete nasal packing and nasal packing with airways (uni/bilateral) on blood pressure, arterial oxygen saturation, middle ear pressure, and post-operative subjective complaints. METHODS: Ninety patients who underwent bilateral anterior nasal packing for epistaxis or following nasal surgery were divided into three equal groups by randomization. Group A received bilateral complete nasal packing, without an airway. In the other two groups, an airway designed from a poly-vinyl chloride, uncuffed endotracheal tube (number 5) was placed below the nasal pack between the inferior turbinate and septum on one (Group B) or both sides (Group C) of the nasal cavity. Patients were monitored in the ward when asleep, especially overnight, for blood pressure and SpO2 levels. RESULTS: Almost all patients in Group A had nasal obstruction with dry mouth, difficulty swallowing, and disturbed sleep. Only 33-40% patients in Groups B and C had similar complaints. Blood pressure rose > 20 mm of Hg in 20 (67%) patients in Group A, while no patients in the airway groups showed any change in blood pressure. In Group A, the average SpO2 during sleep decreased > 4% from baseline in 10 (33%) patients and negative middle ear pressure was found in 5 (17%) patients. The SpO2 and middle ear pressure was within normal limits for all patients with airway packing. CONCLUSION: Nasal packing with an airway may help to reduce post operative morbidity and reduce the risk of hypoxemia.

Comparison between confocal scanning laser tomography, scanning laser polarimetry and optical coherence tomography on the ability to detect localised retinal nerve fibre layer defects in glaucoma patients.

BACKGROUND/AIM: To compare the ability of confocal scanning laser tomography (CSLT), scanning laser polarimetry (SLP) and optical coherence tomography (OCT) in recognising localised retinal nerve fibre layer (RNFL) defects. METHODS: 51 eyes from 43 patients with glaucoma were identified by two observers as having RNFL defects visible on optic disc photographs. 51 eyes of 32 normal subjects were used as controls. Three masked observers evaluated CSLT, SLP and OCT images to determine subjectively the presence of localised RNFL defects. RESULTS: Interobserver agreement was highest with OCT, followed by SLP and CSLT (mean kappa: 0.83, 0.69 and 0.64, respectively). RNFL defects were identified in 58.8% of CSLT, 66.7% of SLP and 54.9% of OCT (p = 0.02 between SLP and OCT) by at least two observers. In the controls, 94.1% of CSLT, 84.3% of SLP and 94.1% of OCT scans, respectively, were rated as normal (p = 0.02 between CSLT and SLP, and SLP and OCT). CONCLUSION: Approximately 20-40% of localised RNFL defects identified by colour optic disc photographs are not detected by CSLT, SPL or OCT. SLP showed a higher number of false-positive results than the other techniques, but also had a higher proportion of correctly identified RNFL defects in the glaucoma population.

A study of acute febrile encephalopathy with special reference to viral etiology.

OBJECTIVE: To study the etiological profile of patients with acute febrile encephalopathy syndrome focusing chiefly on the viral etiology, and to correlate clinical and radiological features of patients with viral encephalitis. METHODS: A prospective hospital based study conducted on the consecutive patients admitted in a pediatric unit during the period of 1(st) February 2004 to 31st January 2005 based on the following inclusion criteria: (1) Age more than 1 month and less than 18 years and (2) A diagnoses of acute febrile encephalopathy, based on the following criteria: (i) fever (ii) acute depression of consciousness or mental deterioration for more than 12 hours with or without motor or sensory deficit and (iii) Total duration of illness at the time of admission 1 week or less. RESULTS: The final study group comprised of 151 patients with mean age of 3.21 +/- 2.9 (range of mth-13 years) and male: female ratio of 1.71: 1. A diagnosis other than viral encephalitis was reached in 94 patients (62.3 %). Pyogenic meningitis was the most frequent diagnosis 51(33.8 %) followed by tubercular meningitis 12 (7.9 %), and cerebral malaria 8 (5.2 %) in the patient group of non-viral causes. Fifty-seven cases (37.3%) were suspected as viral encephalitis and mean age of the cases suspected as viral encephalitis was 2.8 +/- 2.9 (Range 1 mth-10 yrs) with male: female ratio of 1.28: 1. Etiological diagnosis was reached or considered probable in 41 (72%) cases out of the suspected patients. The most common etiological agent identified was enterovirus 71 in 20 patients (35.1 %). The other viruses identified were mumps in 6 (10.5%), Japanese encephalitis in 5 (8.7%), and measles in 4 (7%) cases. MRI brain was done in 39 patients and was abnormal in 14 patients. Out of 57 cases of suspected viral encephalitis 10 patients expired within 48 hours, 2 > 48 hours and 19 atients had significant neurological sequels at discharge. CONCLUSION: The etiology of acute febrile encephalopathy varies from infectious etiologies to noninfectious metabolic disorders. There are no distinguishing clinical or radiological features to differentiate the various causes of viral encephalitis. The clinical and the radiological findings in encephalitis should be interpreted in the geographical and other epidemiological background.

Practical recommendations for measuring rates of visual field change in glaucoma.

To date, there has been a lack of evidence-based guidance on the frequency of visual field examinations required to identify clinically meaningful rates of change in glaucoma. The objective of this perspective is to provide practical recommendations for this purpose. The primary emphasis is on the period of time and number of examinations required to measure various rates of change in mean deviation (MD) with adequate statistical power. Empirical data were used to obtain variability estimates of MD while statistical modelling techniques derived the required time periods to detect change with various degrees of visual field variability. We provide the frequency of examinations per year required to detect different amounts of change in 2, 3 and 5 years. For instance, three examinations per year are required to identify an overall change in MD of 4 dB over 2 years in a patient with average visual field variability. Recommendations on other issues such as examination type, strategy and quality are also made.

In vitro activity of uva-ursi against cytochrome P450 isoenzymes and P-glycoprotein.

Some natural health products (NHPs) affect drug metabolism enzymes and transport proteins, potentially affecting the safety and efficacy of the drug or other NHPs. This study was undertaken to characterize the effect of uva-ursi (Arctostaphylos uva-ursi) on cytochrome P450 isozyme (3A4, 3A5, 3A7, 2C19, and 19)-mediated metabolism and P-glycoprotein (P-gp) transport. Three bulk and 2 capsulated uva-ursi samples were obtained from commercial outlets. The capsules were batched, and herbal samples were ground to a common consistency. Aqueous and methanol extracts were freshly prepared. Cytochrome P450 isozyme-mediated metabolism was determined by using in vitro bioassays. P-gp transport function was determined by using a rhodamine 123 (Rh123) uptake test in human (THP-1) monocytes and human Caco-2 cells. All products were analyzed by HPLC for arbutin, gallic acid, myricitrin, and isoquercetin. A large variation was observed in the biomarkers found between the bulk and capsulated samples. Our data indicate that both the aqueous and methanol extracts of all 5 uva-ursi products showed high cytochrome P450 isozyme inhibition, with the exception of the methanol extracts against cytochromes P3A4 and P19, which had low to moderate activity. The aqueous extracts of uva-ursi showed an inhibitory effect on Rh123 efflux by P-gp at 1 h and an inductive effect at 18 h for both cell lines. Our results show that the uva-ursi herbal products tested here have pharmacological properties, including the potential capacity to affect drug safety and efficacy. Further studies are warranted against a wider range of cytochrome P450 isozymes and to determine whether these effects are clinically significant.

The effect of ABCB1 polymorphism on the pharmacokinetics of saquinavir alone and in combination with ritonavir.

This genotype panel study investigated the effect of ABCB1 polymorphism in exon 26 (C3435T), exon 21 (G2677T/A), and exon 12 (C1236T) on saquinavir pharmacokinetics and on the expression and activity of P-glycoprotein (P-gp) in peripheral blood monocytic cells (PBMCs). One hundred and fifty healthy volunteers were genotyped to identify 15 TT3435 and 15 CC3435 individuals. In these individuals, saquinavir pharmacokinetics were assessed after administration of a single oral dose of saquinavir 1,000 mg and saquinavir/ritonavir 1,000/100 mg. PBMC P-gp expression and activity were assessed in 15 and 19 subjects. The co-administration of ritonavir on study day 2 caused a significant increase in saquinavir exposure, in both TT3435 and CC3435 individuals. No correlation was observed between the ABCB1 C3435T, G2677T/A, and C1236T polymorphisms, separately and in haplotypes, with saquinavir pharmacokinetics, administered with or without ritonavir and with PBMC P-gp expression and activity. In conclusion, ABCB1 polymorphism has no pronounced effect on saquinavir exposure.

Confocal laser Doppler flowmeter measurements in a controlled flow environment in an isolated perfused eye.

The aim of this study was to improve our ability to interpret and validate Heidelberg Retina Flowmeter (HRF) flow images by recording flow measurements from specific regions of the retinal vasculature by taking advantage of the ability to precisely regulate perfusion flow in an isolated eye preparation. The retinal vasculature in 16 isolated perfused pig eyes was perfused with a 50%/50% Krebs/RBC solution at known flow rates ranging from 0 to 300 microl min(-1). At each flow rate, HRF images were obtained at a location approximately two disc diameters from the disc. After HRF image acquisition, the retinal vasculature was perfused with fluorescein isothiocyanate for fluorescence microscopy. Using the standard HRF software and a 10 x 10pixel measurement window, flow rates were measured from a retinal artery, vein, arteriole, venule, and the retinal capillary bed and a capillary-free-zone. The relationship between HRF measured flow and perfusion flow in the different measurement locations was determined. At zero perfusion flow the measured HRF flow was consistently greater than zero ( approximately 170 arbitrary units (AU)), and not significantly different at each measurement location except for the retinal vein, which had a significantly higher HRF flow value ( approximately 230AU). At higher perfusion flow rates the flow signal from the larger vascular elements (arteries and veins) increased rapidly thereafter to reach several thousand AU at a total perfusate flow of 50 microlmin(-1) and increased less rapidly at higher flow rates. In arterioles, the HRF flow was more linear over a broader range of perfusate flow rates but the peak flow signal was an order of magnitude smaller than that from the retinal artery. Both the linearity and magnitude of the flow signal in venules was less than that in arterioles. In capillary areas and in the capillary free zone, the HRF flow showed only a very weak relationship to perfusion flow when compared to the background noise. The choice of location for HRF flow analysis greatly influences the ability of the technique to measure changes in retinal blood flow. The major arteries and veins provide the strongest signal and greatest signal to noise ratio. However, the retinal arterioles produce an HRF signal that is more linear over a wider range of perfusate flow rates.

Central corneal thickness and progression of the visual field and optic disc in glaucoma.

AIMS: To determine whether central corneal thickness (CCT) is a significant predictor of visual field and optic disc progression in open angle glaucoma. METHODS: Data were obtained from a prospective study of glaucoma patients tested with static automated perimetry and confocal scanning laser tomography every 6 months. Progression was determined using a trend based approach called evidence of change (EOC) analysis in which sectoral ordinal scores based on the significance of regression coefficients of visual field pattern deviation and neuroretinal rim area over time are summed. Visual field progression was also determined using the event based glaucoma change probability (GCP) analysis using both total and pattern deviation. RESULTS: The sample contained 101 eyes of 54 patients (mean (SD) age 56.5 (9.8) years) with a mean follow up of 9.2 (0.7) years and 20.7 (2.3) sets of examinations every 6 months. Lower CCT was associated with worse baseline visual fields and lower mean IOP in the follow up. In the longitudinal analysis CCT was not correlated with the EOC scores for visual field or optic disc change. In the GCP analyses, there was a tendency for groups classified as progressing to have lower CCT compared to non-progressing groups. In a multivariate analyses accounting for IOP, the opposite was found, whereby higher CCT was associated with visual field progression. None of the independent factors were predictive of optic disc progression. CONCLUSIONS: In this cohort of patients with established glaucoma, CCT was not a useful index in the risk assessment of visual field and optic disc progression.

Effects of minocycline and tetracycline on retinal ganglion cell survival after axotomy.

In the present study, we compared the in vivo neuroprotective efficacy of intraperitoneally administered tetracycline and minocycline to enhance the survival of retinal ganglion cells (RGCs) following unilateral axotomy of the adult rat optic nerve. We also examined the effects of the tetracycline drugs on the activation of retinal microglia. RGCs in retinal whole-mounts were visualized by retrograde labeling with fluorogold. The presence of activated microglia was confirmed immunohistochemically using OX-42 monoclonal antibodies. Optic nerve axotomy produced RGC death and increased activation of microglia. No significant RGC loss was seen prior to 5 days and approximately 50% and 80-90% cell loss occurred at 7 and 14 days, respectively. Examination of the effects of tetracycline and minocycline on RGC survival at 7 days post-axotomy, revealed increased numbers of RGCs in minocycline-treated animals (75% of non-axotomized control) compared with vehicle-only (52% of control) and tetracycline-treated (58% of control) animals. The densities of RGCs (RGCs/mm2+/-S.D.) for control, vehicle-, tetracycline- and minocycline-treated axotomized animals were 1996+/-81, 1029+/-186, 1158+/-190 and 1497+/-312, respectively. The neuroprotective effect of minocycline seen at 7 days was transient, since RGCs present in minocycline-treated animals at 14 days post-axotomy (281+/-43, 14% of control) were not significantly different to vehicle-treated animals (225+/-47, 11% of control). OX-42 staining of activated retinal microglia was reduced in tetracycline- and minocycline-treated axotomized animals compared with axotomized animals receiving vehicle-only. These results demonstrate that systemic administration of the second-generation tetracycline derivative, minocycline, delays the death of axotomized RGCs by a mechanism that may be associated with inhibition of microglia activation. The neuroprotective efficacy of minocycline following optic nerve axotomy was superior to that of tetracycline.